Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy

Abstract

Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-α, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and non-phosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response.

A novel curcumin derivative for the treatment of diabetic neuropathy

“…AMPK depletion has been linked to impaired axonal bioenergetic profile in diabetes (Roy Chowdhury et al, 2012). Moreover, the AMPK activator met-formin both protects nerve conduction and diminishes pro-inflammatory markers such as TNFα and plasma CRP in diabetic rats (Hasanvand et al, 2016) and we found similar effects of J147 on these indices of inflammation. While further studies are required to determine the precise neuroprotective mechanisms of J147 in diabetic neuropathy, efficacy of this curcumin derivative against MNCV slowing supports advancement to clinical investigation.…”

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

“…Kooy et al studied the effect of Metformin added to insulin therapy in 390 patients with type 2 DM and macro- and microvascular complications; they discovered that Metformin reduced macrovascular complications at 4.3 years of follow-up, although no beneficial effects on DPN were observed [126]. Recently, Hasanvand et al demonstrated that the activation of AMP kinase signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response, and Metformin reduced the levels of inflammatory cytokines in diabetic rats; it also improved motor nerve conduction velocities of the sciatic nerves [127]. …”

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats

“…AMP-activated protein kinase (AMPK) activity plays a vital role in mediating hepatic lipogenesis[18]. Recent studies have shown that AMPK activity is reduced by the factors implicated in the development of NAFLD, such as inflammation and obesity[19,20]. Therefore, inhibition of hepatic lipogenesis by AMPK activation is envisaged as a viable therapeutic strategy to prevent the initiation and progression of NAFLD[21].…”